The role of routine surveillance imaging (RSI) in first complete remission (CR1) for peripheral T-cell lymphoma (PTCL) patients is unclear. Theoretically, RSI should allow for the earlier detection of asymptomatic relapses, thus leading to the earlier initiation of second line therapy. In an abstract presented during a session of the 2014 ASCO conference, we investigated the proportion of PTCL relapses detected by RSI and those found through clinical finding, before comparing the outcomes in patients from those two groups.

341 patients were retrospectively identified through the T-cell lymphoma databases of the National Cancer Centre Singapore/Singapore General Hospital and Weill-Cornell Medical College. These patients were divided into groups based on their mode of relapse detection; through RSI or clinical findings. PTCL subtypes included PTCL-NOS, AITL, ALCL (ALK positive and negative), EATL, GDT, HSTL and ATLL, while patients with leukemias, indolent, composite and cutaneous lymphomas were excluded. Of the 341 patients, 145 patients achieved CR1 and 64 relapsed. Relapses were detected by clinical findings in 51 patients, RSI in 9 patients and only 3 patients did not have any clinical findings at the time of relapse.

This data from our findings suggests that RSI does not often impact the detection of CR1 in patients with PTCL.

The peripheral T-cell lymphomas (PTCL) are uncommon lymphoid diseases that account for 5-10% of all non-Hodgkin lymphomas in adults in North America. Compared to B-cell non-Hodgkin lymphomas, the PTCLs are generally aggressive and less responsive to current treatment options. Relapsed and refractory diseases are common. Novel and target therapies are in much need to improve quality and duration of response. At the 2012 American Society of Hematology (ASH) meeting in Atlanta, several research groups reported encouraging study results with the antibody-drug conjugate Brentuximab vedotin for T-cell lymphomas. Brentuximab vedotin (BV) is an anti-CD30 chimeric antibody conjugated by a protease-cleavable linker to the microtubule-disrupting agent monomethyl auristatin E. BV received accelerated FDA approval in 2011 for relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), 2 diseases that express abundant CD30. Several new studies have looked at the treatment outcome of BV in patients with systemic or cutaneous T-cell lymphomas that express variable amount of CD30.

Studies in Systemic T-cell Lymphomas

Dr. Jacobsen from Dana Farber Cancer Institute reported an interim analysis of a phase II multicenter study which evaluated the antitumor activity of BV in patients with relapsed or refractory CD30-positive NHL. BV was administered at 1.8 mg/kg every 3 weeks by IV infusion. The study also explored the correlation between antitumor activity and quantitative CD30 expression. Fifty-three patients with various CD30-positive NHLs have been enrolled, including 18 patients with mature T-/NK-cell lymphomas. Of the T-cell lymphoma patients enrolled, 9 have angioimmunoblastic T-cell lymphoma (AITL), 8 have PTCL-NOS, and 1 has cutaneous T-cell lymphoma. The ORR was 27% (3/11) for mature T-/NK-cell NHLs. Thus far, response was particularly noteworthy in in AITL where 3 of 5 patients (60%) have responded (2 CR, 1 PR). Treatment-emergent adverse events were generally mild and moderate (grade 1/2), and expected including peripheral neuropathy and cytopenias, which was consistent with the safety profile of BV. CD30 expression levels for patients with a CR or PR were widely variable and ranged from <1% to 90%. Preliminary data seems to suggest that BV may be beneficial for patients with T-cell lymphomas that have low CD30 expression. Dr. Fanale from MD Anderson Cancer Center reported a phase I study with BV administered concurrently with multi-agent chemotherapy as frontline treatment of systemic ALCL and other CD30 positive T-cell lymphomas. The study was Read the rest of this entry »

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for people with relapsed or refractory Peripheral T-Cell Lymphoma (PTCL). The sponsor is Millennium Pharmaceuticals, and the principal investigator at Weill Cornell is Dr. Jia Ruan. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Study Details

The purpose of the study is to assess how well people with PTCL respond to treatment with the experimental drug Alisertib (also known as MLN8237) as compared to other PTCL treatments.

Study participants will be randomly assigned to receive Alisertib or one of the following drugs used to treat PTCL: pralatrexate, romidepsin or gemcitabine.

Alisertib has been developed to interfere with cell division, which is required for normal and cancer cell growth. By blocking an enzyme that cells need to reproduce, alistertib may slow the growth of cancer cells.

The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphoid diseases that constitute less than 15 percent of all non-Hodgkin lymphomas in adults in North America. The most common subtypes are 1) Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); 2) Anaplastic large cell lymphoma, primary systemic type (ALCL); and 3) Angioimmunoblastic T-cell lymphoma (AITL). The PTCLs are generally aggressive, and tend to run a more relapsing and less favorable clinical course compared to B-cell NHLs. Relapsed and refractory diseases are common. Novel and target therapies are in much need.

At the recent Annual Society of Hematology (ASH) meeting, Dr. Friedberg of the University of Rochester reported the result of a phase 2 trial of Alisertib (MLN8237), a potent inhibitor of aurora A kinase, in patients with relapsed aggressive non-Hodgkin’s lymphoma (NHL). Aurora kinases regulate mitosis during cell division. Inhibition of aurora A kinase can lead to mitotic errors and premature cell death. Alisertib is taken orally twice daily for 7 days on 21-day cycles. This phase 2 study enrolled a total of 48 patients, including 8 patients with peripheral T-cell lymphoma. The overall response rate was 32%. Response in T-cell NHL was the most impressive at 57%: four out of eight patients responded, and the some of the responses were durable. The response rates in DLBCL and MCL were modest around 20%. Treatment-related side effects were generally tolerable and included low blood counts, fever, fatigue and inflammation in mouth. Based on these results, additional clinical trials (phase II sponsored by SWOG / NCI and phase III sponsored by Millennium) with this orally available compound are moving forward in T-cell lymphoma. Both of these studies will be available soon at Weill Cornell Medical College (click here to read about the SWOG/NCI trial and click here to read about the Millennium trial on clinicaltrials.gov).